Designing stem-cell-based dopamine cell replacement trials for Parkinson's disease.
Nature Publishing Group
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Barker, R., & TRANSEURO consortium,. (2019). Designing stem-cell-based dopamine cell replacement trials for Parkinson's disease.. Nature medicine, 25 (7), 1045-1053. https://doi.org/10.1038/s41591-019-0507-2
Clinical studies of dopamine cell replacement therapies for Parkinson’s disease (PD) go back more than 30 years. The outcomes using transplantation of human fetal ventral mesencephalic tissue (hfVM) have been variable, with some patients coming off their anti-PD treatment for many years, while other patients have not responded and/or developed significant side effects, including graft-induced dyskinesias. This led to a re-appraisal of how trials should best be done which resulted in a new EU funded allograft trial with fetal dopamine cells across several centres in Europe. This new trial, TRANSEURO1 (NCT01898390); is an open label study in which patients were randomly selected for transplantation out of a larger observational cohort of patients with mild PD undergoing identical assessments. The TRANSEURO trial is currently ongoing, having completed both recruitment into a large multicentre observational study of younger onset early stage PD as well as transplantation of hfVM in 11 patients. While completion of TRANSEURO is not expected until 2021, we feel that sharing the rationale for the design of TRANSEURO, along with lessons we have learned along the way, can help to inform researchers and facilitate planning of human pluripotent stem cell-derived dopamine cell transplants for future clinical trials.
TRANSEURO consortium, Humans, Parkinson Disease, Immunosuppressive Agents, Stem Cell Transplantation, Fetal Tissue Transplantation, Research Design, Clinical Trials as Topic, Dopaminergic Neurons
This study was supported by an EU FP7 grant (242003) as well as funding from the Cure Parkinson’s Trust (RG81537), John Black Charitable Trust and Multipark. The work was also supported by NIHR funding of Biomedical Research Centres at UCL and Cambridge (146281). RAB is an NIHR Senior Investigator (NF-SI-0616-10011) and a PI in the MRC/WT Stem Cell Institute (203151/Z/16/Z).
European Commission (242003)
Cure Parkinson's Trust (Transeuro Follow Up Study)
Cure Parkinson's Trust (RVG9R- p137)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0616-10011)
Wellcome Trust (203151/Z/16/Z)
External DOI: https://doi.org/10.1038/s41591-019-0507-2
This record's URL: https://www.repository.cam.ac.uk/handle/1810/293658
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